Cao Hong, Chen Xiu-Xia, Gui Bo, Wang Jun, Duan Shi-Ming, Zeng Yin-Ming
Department of Anesthesiology, The 2nd Affiliated Hospital of Wenzhou Medical College, Wenzhou 325027, China.
Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2006 Feb;22(1):50-3.
To investigate the effect of diazoxide preconditioning and the role of ERK and JNK in cellular signaling during diazoxide preconditioning protection in isolated spontaneous hypertension rat (SHR) hearts.
Hearts were isolated from male SHR rats, and perfused on a Langendorff apparatus. Five groups were considered (n = 6). Con: after 40 min perfusion the hearts were submitted to 25 min ischemia followed by 30 min reperfusion. IP: the hearts were preconditioned with 2 periods of 5 min ischemia and 10 min reperfusion prior to 25 min ischemia. DP: the hearts were preconditioned with 2 periods of 10 min K-H solution with 50 micromol x L(-1) diazoxide and 5 min K-H solution reperfusion prior to 25 min ischemia. 5-HD: perfuse with 100 micromol x L(-1) 5-HD (a special mitochondrial ATP sensitive potassium channel blocker) for 10 min followed by 30 min K-H solution perfusion before 25 min ischemia. 5-HD + DP: 100 micromol x L(-1) 5-HD was given for 10 min before diazoxide preconditioning.
During reperfusion, comparing with Con group, the recoveries of left ventricle developed pressure (LVDP), + dP/dt(max), - dP/dt(max) and left ventricle end diastolic pressure (LVEDP) were improved in IP and DP groups (P < 0.01 vs Con). At the end of reperfusion, compared with Con group, the expression of ERK in myocardium were higher in IP and DP groups (P < 0.01 vs Con), there was no significance between 5-HD and Con group, but 5-HD couldn't inhibit the expression of ERK induced by diazoxide preconditioning. The expression of JNK in IP and DP groups were decreased (P < 0.05 vs Con), this effect could been inhibited by 5-HD.
These results indicated that diazoxide preconditioning could mimic ischemic preconditioning, the activation of ERK expression and the declining of JNK expression involved in diazoxide preconditioning in isolated SHR hearts.
研究二氮嗪预处理的作用以及细胞外信号调节激酶（ERK）和应激活化蛋白激酶（JNK）在二氮嗪预处理保护离体自发性高血压大鼠（SHR）心脏过程中细胞信号传导中的作用。
从雄性SHR大鼠分离心脏，在Langendorff装置上进行灌注。分为五组（n = 6）。对照组：灌注40分钟后，心脏经历25分钟缺血，随后30分钟再灌注。缺血预处理组：在25分钟缺血前，心脏先经历2个周期的5分钟缺血和10分钟再灌注预处理。二氮嗪预处理组：在25分钟缺血前，心脏先经历2个周期的含50微摩尔/升二氮嗪的K-H溶液灌注10分钟和K-H溶液再灌注5分钟预处理。5-羟癸酸组：在25分钟缺血前，先灌注100微摩尔/升5-羟癸酸（一种特殊的线粒体ATP敏感性钾通道阻滞剂）10分钟，随后进行30分钟K-H溶液灌注。5-羟癸酸+二氮嗪预处理组：在二氮嗪预处理前给予100微摩尔/升5-羟癸酸10分钟。
在再灌注期间，与对照组相比，缺血预处理组和二氮嗪预处理组左心室发展压（LVDP）、+dP/dt（max）、-dP/dt（max）和左心室舒张末期压（LVEDP）恢复情况改善（与对照组相比P < 0.01）。在再灌注结束时，与对照组相比，缺血预处理组和二氮嗪预处理组心肌中ERK表达较高（与对照组相比P < 0.01），5-羟癸酸组与对照组无显著差异，但5-羟癸酸不能抑制二氮嗪预处理诱导的ERK表达。缺血预处理组和二氮嗪预处理组JNK表达降低（与对照组相比P < 0.05），此效应可被5-羟癸酸抑制。
这些结果表明，二氮嗪预处理可模拟缺血预处理，离体SHR心脏中二氮嗪预处理涉及ERK表达的激活和JNK表达的下降。
